[{"id":"lotis2-ep1","name":"Overall response rate (ORR)","type":"PRIMARY","unit":"%","results":[{"ci":"39.9-56.7","arm":"lotis2-lonca","label":"48.3% (70/145)","value":48.3}],"description":"Proportion achieving complete or partial response. In heavily pretreated 3L+ DLBCL patients (median 3 prior therapies), any response is meaningful given limited options."}]

GGT increase 41.4% (17.2% Gr>=3). Neutropenia 40% (26.2% Gr>=3). Thrombocytopenia 33.1% (17.9% Gr>=3). Edema/effusion composite 31% (Gr3 edema 3%, Gr3 pleural effusion 3%). Liver enzyme abnormalities composite 51%. Skin/nail reactions 43%. 19% permanently discontinued due to AEs (10.3% for GGT, 2.8% edema, 2.8% effusion).

Zynlonta has accelerated US approval and conditional EU approval. LOTIS-5 is the confirmatory Phase 3 trial. The 48.3% ORR and 24.8% CR in 3L+ is clinically meaningful but the PFS/OS are modest. GGT elevation is the signature safety signal. Key debate: will LOTIS-5 convert to full approval or will bispecifics/CAR-T erode the market?

ADC targeting CD19 (broadly expressed on B-cell malignancies) conjugated to PBD dimer payload. PBD creates DNA interstrand crosslinks - more potent payload than MMAE (used by Polivy).